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Metabolism and Health Effects of Lactose and Galactose
Corinna Walsh (RD) PhDPresented by
Louise van den Berg
Pretoria CNE 18 October 2017
Introduction
Scientific evidence supports the essential role of
milk and dairy products as part of a healthy eating pattern
• Dairy foods are excellent sources of thenutrients calcium, magnesium, potassium, protein and carbohydrates
• Benefits of milk and other dairy foods for bone and dental health are well-known
• Dairy intake also linked to other health benefits
• Key role in development throughout life
Visioli and Strata, 2014; Hirahatake et al., 2014; Pereira, 2014; Keast et al.,
2013; Prado and Dewey, 2014; Weaver, 2014; Rice et al., 2013
Hypothesize that galactose from lactose in milk may induce:
• oxidative stress chronic low grade inflammation
• a decreased immune response and
• neurodegeneration
Michaëlsson et al., 2014; Cui et al., 2006
Criticisms
• Possibility of reverse causation (women who knew that
they had osteoporosis may have consumed more milk)
• Multivariate model did not adjust for osteoporosis or
bone mineral density
• Large sex differences not accounted for
• Vit D status may have impacted on fracture risk and all-
cause mortality
• Synthetic substances used in milk production at the
time that cohorts were recruited may have impacted on
mortality
Michaëlsson et al., 2014; Labos and Brophy, 2014; Bonneux, 2014; Hill, 2014;
Sundar, 2014
Aim of presentation
• In view of the mentioned limitations and in the
absence of evidence from randomized controlled
trials (RCTs), the results of the Michaëlsson study
need to be interpreted with caution
• Yet, the study has cast doubt on the health
benefits of milk
• This presentation will aim to evaluate the
evidence on the health effects of dairy, with
special reference to lactose and its metabolites,
which are naturally present in milk
Content
Composition, digestion, absorption and
metabolism of lactoseLactose intolerance
Lactose as a prebiotic Lactose in calcium absorption
Non-communicable diseases:
Type 2 Diabetes Mellitus
Hypertension
Dental caries
Composition, digestion, absorption and metabolism of lactose
• Lactose consists of galactose bound to glucose
• The enzyme lactase is needed to hydrolyse lactose to
glucose and galactose to facilitate absorption and
transport across the intestinal mucosa
• Galactose and glucose are absorbed and actively transported
from the intestinal lumen into the blood by the sodium-
dependent hexose transporter, SGLT1
Deng et al., 2015; Coelho et al., 2015; Schaafsma, 2008
They are then passively transported from the blood into the
liver by the GLUT-2 transporter
• Galactose is then
phosphorylated in the liver
and finally converted into
glucose
• Glucose tends to pass
through the liver and can be
metabolised anywhere in the
body as a source of energy
Deng et al., 2015; Coelho et al., 2015; Schaafsma, 2008
Galactose
• Galactose is metabolized to glucose by
3 enzymes in the Leloir pathway, the
main pathway of galactose metabolism
• These enzymes are:
• galactokinase (GALK)
• galactose-1 phosphate uridylyltransferase
(GALT) and
• UDP-galactose 4’-epimerase (GALE)
• Although this pathway occurs mostly in
the liver, it is also active in cells in the
brain, lens of the eye and ovaries
Coelho et al., 2015; Lukito et al., 2015
Galactose
• The presence of galactose in
bacteria, plants and animals
confirms its importance for
living organisms
• It is found in lactose as well as
in complex carbohydrates,
including oligosaccharides and
polysaccharides, glycoproteins
and glycolipids
Coelho et al., 2015
Functions of Galactose
Apart from its importance in energy
production:
• Referred to as ‘brain sugar’ in lay terms
owing to its role in supporting brain
structure and development during the
neonatal period and early life
• Important role in maintaining a healthy GIT
- present in the raffinose-family
oligosaccharides that stimulate growth of
some intestinal microflora
• Display anti-adhesive activity - inhibit
infections by enteric pathogens
Prado and Dewey, 2014; Schaafsma, 2008; Zivkovic and Barile, 2011
Galactosemia
• A congenital disorder involving one of the
three enzymes in the Leloir pathway -
classic galactosemia is due to a GALT
deficiency
• Particularly serious during the neonatal
period and affects a number of organs,
including the liver and brain
• Dietary restriction of galactose resolves
the symptoms of galactosemia, but
• Associated with severe long-term
complications cognitive and fertility
impairments, even in patients who follow a
galactose-restricted diet rigorously
Lukito et al., 2015; Waisbren et al., 2012
Lactose intolerance
• Under normal conditions,
lactase is produced in the
intestinal mucosa of
mammals
• Full-term newborn infants
generally have sufficient
lactase activity to digest
milk
Deng et al., 2015; McSweeney and Fox, 2009; Vandenplas, 2015; Heaney, 2013;
Mattar et al., 2012; Brown-Esters et al., 2012; Leonardi et al., 2012
Lactose intolerance
• However, lactase activity declines after weaning in most humans
(lactase non-persistence), especially those from East Asian and
African heritage, resulting in lactose maldigestion
Deng et al., 2015; McSweeney and Fox, 2009; Vandenplas, 2015; Heaney, 2013;
Mattar et al., 2012; Brown-Esters et al., 2012; Leonardi et al., 2012
Deng et al., 2015; McSweeney and Fox, 2009; Vandenplas, 2015; Heaney, 2013;
Mattar et al., 2012; Brown-Esters et al., 2012; Leonardi et al., 2012
Lactose intolerance refers to the digestive symptoms
that are associated with lactose maldigestion
• abdominal
• discomfort,
• nausea,
• cramps,
• bloating,
• flatulence,
• diarrhoea
Lactose intolerance
Those who consider
themselves lactose intolerant
may decrease their dairy
intake, resulting in
compromised intake of the
nutrients and other beneficial
compounds in dairy
Bailey et al., 2013
Strategies to improve lactose intolerance
• A low lactose load (<6 g present
in half a serving of milk) is
unlikely to cause symptoms
• Using small amounts of dairy at
a time, or taking milk with a
meal, slows the release of
lactose into the intestine, which
reduces the load to be digested
- less discomfort
Vandenplas, 2015; Heaney, 2013; Brown-Esters et al., 2012; Suchy et al., 2010
Strategies to improve lactose intolerance
• Dairy foods such as cheese (especially hard cheeses), active-
culture yoghurt and fermented products such as buttermilk
contain limited lactose and can be eaten without causing
gastrointestinal discomfort
• These foods are fermented by lactic acid bacteria, which
convert some of the lactose to lactic acid during production
Vandenplas, 2015; Heaney, 2013; Brown-Esters et al., 2012; Suchy et al., 2010
Strategies to improve lactose intolerance
• Although more expensive,
reduced-lactose or lactose-free
milk is also available - this milk
has many health benefits over
dairy substitutes such as soy milk
• Taking a lactase tablet with milk
improves digestion
• Probiotics that include lactase-
containing organisms can help to
relieve symptoms
Vandenplas, 2015; Heaney, 2013; Brown-Esters et al., 2012; Suchy et al., 2010
Strategies to improve lactose intolerance
• Tolerance can be built up gradually over a
period of time:
• consuming lactose-containing foods encourages
an intestinal flora population with active
lactase
• intake can be increased gradually by, for
example, adding half a glass of milk to one meal
on the first day, half a glass to two meals on the
next day, etc.
• Chocolate milk is better tolerated than
white (higher osmolality or energy content)
Vandenplas, 2015; Heaney, 2013; Brown-Esters et al., 2012; Suchy et al., 2010
There may an evolusionary
reason why only about 35%
of the human population can
digest lactose beyond the
age of about 7 / 8 years
Effects of lactose as a prebiotic
• The recent emphasis on the structure and
function of the human microbiome has
focused attention on the potential role of
probiotics and prebiotics in promoting
health
• Prebiotics are non-digestible compounds
that stimulate the growth and activity of
the bacteria in the digestive system
• Lactose and oligosaccharides in milk are
considered to be bioactive ingredients
that may create a healthy microbiota
owing to their bifidogenic effects
Petschow et al., 2013; Lukito et al., 2015; Visioli and Strata, 2014; Vandenplas,
2015; Hirahatake et al., 2014; Zivkovic and Barile, 2011
Effects of lactose as a prebiotic
Lactose is not fully digested and thus
proceeds to the colon where it exerts
prebiotic effects
Most lactose will be digested in the
small intestine, but some may reach the
large intestine and serve as a prebiotic
for the colonic microbiota, including
lactic acid bacteria
Lukito et al., 2015; Venema, 2012
Lactose non-persistent persons
Lactase-persistent persons
Effects of lactose as a prebiotic
The colonic microbiota hydrolyse and ferment lactose in the
colon, producing metabolites such as short-chain fatty acids
(primarily acetate, propionate and butyrate) and gases
Lukito et al., 2015; Venema, 2012
Lactose and oligosaccharides
Vandenplas, 2015; Vulevic et al., 2015; Eiwegger et al., 2004; Hickey, 2012; Flint et al., 2012; Zivkovic and Barile, 2011
Effects of lactose as a prebiotic
• Dairy prebiotics and probiotics may influence gut microbiota in
such a way that insulin sensitivity and the action of the incretin
hormone glucagon-like peptide (GLP-1) are positively affected
Vandenplas, 2015; Vulevic et al., 2015; Eiwegger et al., 2004; Hickey, 2012; Flint
et al., 2012; Zivkovic and Barile, 2011
Effect of lactose on calcium absorption
Heaney and Nordin, 2002; Vandenplas, 2015; Kwak et al., 2012; Abrams et al.,
2002
Effect of lactose on calcium absorption
• Net calcium absorption about 10-30% of intake
• Animal studies: lactose has a positive effect on intestinal calcium absorption
• Effect in humans has not been confirmed (probably owing to potential confounding factors such as other dietary components that may affect calcium absorption)
Heaney and Nordin, 2002; Vandenplas, 2015; Kwak et al., 2012; Abrams et al.,
2002
Effect of lactose on calcium absorption
• Lactose does show enhanced
absorption of calcium in humans
compared with other types of non-
absorbable sugars (such as
mannitol, lactitol or corn starch)
• Absorption of calcium significantly
higher in infants fed a lactose-
containing formula than in those fed
a lactose-free formula that
contained corn maltodextrin and
corn syrup solids
Heaney and Nordin, 2002; Vandenplas, 2015; Kwak et al., 2012; Abrams et al.,
2002
Effect of lactose on calcium absorption
The exact mechanism by which lactose enhances the
absorption of calcium unclear:
• may be due to an effect on intestinal alkaline phosphatase
• increased mineral solubility
• enhanced osmotic pressure following fermentation
Kwak et al., 2012; Areco et al., 2015; Schaafsma, 2008
Effect of lactose on calcium absorption
In persons with lactase non-persistence, calcium
absorption from dairy products is enhanced due to the
prebiotic effect of lactose:
• sustaining the growth of gut flora such as bifidobacteria
and lactobacilli
• encouraging the formation of short-chain fatty acids that
promote the growth of lactic acid bacteria
Kwak et al., 2012
So, yes…there are apparent
advantages to being lactose
non-persistence after all…
Why are some people lactose non-persistence and others not?
Originally milk was
not tolerated >7-8yrs
After the onset of
cattle farming
Developed ways to
tolerate milk by
fermenting it
In Europe 7500 yrs ago:
a single gene mutation
emerged that caused
lactose persistence
Curry, 2013, Nature, 500
In Europe the DNA base cytosine changed to thymine in a
genomic region (LP allele) not far from the lactase gene
Pockets of lactase persistence in
West Africa, Middle East and South
Asia due to different mutations
(213910*T)
Why did the mutation persist?
1. Opened up a new nutrient rich food source
2. When the LP allele appeared, it offered a major selective advantage -> how?
Still debated….
-vit D?
- malaria?
In a 2004 study researchers estimated that people with the mutation would have produced up to 19% more fertile offspring than those who lacked it.
Compounded over several hundred generations,
that advantage could help a population to take
over a continent. But only if “the population has
a supply of fresh milk and is dairying”
“It’s gene–culture co-evolution. They feed off
of each other.”
Curry, 2013, Nature, 500
Niche construction
Laland, K. N., Olding-Smee, F. J. & Feldman, M. W. 1996 J. Evol. Biol. 9, 293–316.
A growing evidence base supports the inverse association
between dairy consumption and health outcomes
Dairy : Chronic diseases of lifestyle?
• Studies often heterogeneous:
• Various study designs have been
applied, including observational
studies (cross-sectional and
longitudinal cohort studies),
RCTs, systematic reviews and
meta-analyses
• Studies do not differentiate on
the basis of health status,
weight, age or ethnic
background
• Studies often heterogeneous (cont.):
• Although differences in nutrient composition of dairy products may affect outcomes differently, some studies evaluated the effect of total dairy product intake, whereas others differentiated between low-fat dairy products, high-fat dairy products, yoghurt, cheese, and liquid versus solid foods
• Other factors that may impact on health outcomes and which should ideally be adjusted for include smoking, alcohol consumption and other dietary confounders (such as calcium and total energy intake)
Overweight and obesity: Evidence
• Confirmed that an
energy-restricted diet
that includes increased
milk and dairy
consumption lowered
body weight and body
fat in the short term
• However, in situations
without energy
restriction, inclusion of
dairy was unlikely to
impact on body weight
Chen et al. (2012): 27 RCTs, 2101 participants
Overweight and obesity: Evidence
Kratz et al. (2013):
16 observational studies
• Relationship between dairy fat and
high-fat dairy foods, obesity and
cardio-metabolic disease
• In 11 of the 16 studies, high-fat
dairy intake was inversely
associated with measures of
adiposity
Overweight and obesity: Evidence
Abargouei et al. (2012):
14 RCTs, 883 participants
• Including dairy products in
weight-loss diets, reduced fat
mass and waist circumference
and accelerated weight
reduction, while increasing lean
mass significantly more than
conventional weight-loss diets
Overweight and obesity: Evidence
Dror (2014):
36 cross-sectional, prospective cohort and intervention studies
amongst pre-school children, school-age children and adolescents
in developed countries
• In adolescents, dairy intake was inversely associated
with adiposity, while the association was not significant
in school-age or pre-school children
Overweight and obesity: Evidence
Louie et al. (2011):
19 cohort studies (10 in
children and adolescents and 9
in adults)
A beneficial effect was found
in 8 studies, whereas 7
showed no effect, 1 reported
an increased risk (amongst
children) and 2 reported both
a decreased and increased
risk, depending on the type
of dairy eaten
Overweight and obesity: Evidence
Lu et al. (2016):
10 cohort studies (46 011
children and adolescents)
Dairy consumption was
inversely associated with body
fat and positively associated
with an increased BMI,
indicating that dairy products
may promote lean body mass
but decrease body fat and so
increase BMI
Overweight and obesity: Mechanisms
• A high calcium intake may lead to the calcium-mediated formation of insoluble soaps, which prevent fat absorption by binding bile acids
• Whey protein seems to have an important role in muscle sparing and lipid metabolism
• Dairy may induce reduced lipogenesis and increased lipolysis
• Lactose may influence the bacterial composition of the gut microbiota, influencing energy homeostasis and insulin sensitivity as well as fat storage and metabolism
Chen et al., 2012; Kratz et al. 2013; Zemel, 2009; Christensen et al., 2009; Weaver,
2014; Rice et al., 2013; Sanders, 2012; Sousa et al., 2012; Pal et al., 2010; Petschow
et al., 2013; Velagapudi et al., 2010
“The application of prebiotics and probiotics in
manipulating the microbiota to improve lipid
metabolism and insulin resistance is a field of research
that may come to have an important role in addressing
overweight and obesity”
Petschow et al.,2013
Type 2 Diabetes Mellitus: Evidence (6)
Elwood et al. (2):
4 prospective cohort
studies
Milk or dairy consumption
protected against T2DM
Each additional serving
per day was significantly
associated with a
reduction of 4–9% in
diabetes incidence
Type 2 Diabetes Mellitus: Evidence
Pittas et al. (2007) cohort
studies
• Compared the effect of
high and low dairy intakes
(3–5 servings per day vs
1.5 servings per day)
•Higher dairy intake was
associated with a lower
risk of diabetes
Type 2 Diabetes Mellitus: Evidence
Kratz et al. (2013)
• Consumption of high-fat
dairy products was inversely
associated with T2DM
• Same association was not
found for low-fat dairy
Type 2 Diabetes Mellitus: Evidence
Tong et al. (2011):
seven cohort studies
(328 029 cases)
• Inverse association
between yoghurt and
milk consumption
(especially skimmed or
semi-skimmed milk)
and type 2 diabetes,
which seemed to be
dose dependent
Type 2 Diabetes Mellitus: Evidence
Aune et al. (2013):
17 prospective cohort
and case–control
studies
• Significant inverse
association between
intakes of dairy
products and the risk
of type 2 diabetes
Type 2 Diabetes Mellitus: Evidence
Gao et al. (2013):
14 studies
• To clarify the dose–response
association of dairy intake and
risk of T2DM
• Inverse linear association of
consumption of all dairy products
(13 studies), low-fat dairy
products (8 studies), cheese (7
studies) and yoghurt (7 studies)
and the risk of type 2 diabetes
Type 2 Diabetes Mellitus: Mechanisms
• A beneficial effect of dairy on metabolic and
inflammation markers relevant to T2DM and
insulin resistance found in animal studies
• Dairy fat - trans-palmitoleic acid - may
improve insulin secretion, triglyceridaemia
and blood pressure
• Relatively low glycaemic index of milk assists
in blood glucose control
• Lactose may have beneficial effects on the
gut microbiota which may affect GLP-1 and
gastric inhibitory polypeptide (GIP), both of
which are affected in T2DM
Hirahatake et al., 2014; Kalergis et al., 2013; Kratz et al., 2013; Mozaffarian
et al., 2013; Sluijs et al., 2012; Gunnerud et al., 2012; Panwar et al., 2013
Hypertension: Evidence
Appel et al., 1997:
Dietary Approaches to Stop
Hypertension (DASH) trial
• A diet rich in fruit, vegetables
and low-fat dairy, with reduced
total and saturated-fat intake
reduces blood pressure
• About 50% of the reduction in
blood pressure associated with
the DASH diet ascribed to dairy
consumption
Hypertension: Evidence
McGrane et al. (2011):
RCTs and cohort
studies
• Significant inverse
associations between
intakes of total dairy,
low-fat dairy and fluid
dairy foods and
hypertension, but none
for high-fat dairy and
cheese
Hypertension: Evidence
Ralston et al. (2012):
5 cohort studies, 45 000 subjects of whom
11 500 had elevated blood pressure
• Significant inverse associations between
intakes of total dairy, low-fat dairy and
fluid dairy foods (milk and yoghurt) and
blood pressure
• Fat-free and low-fat dairy products,
especially milk, appear to have an even
more significant lowering effect on blood
pressure than other dairy products
Hypertension: Evidence
Soedamah-Muthu et al. (2012):
dose–response meta-analysis of cohort studies, 57 256
subjects (of whom 15 367 were hypertensive)Followed up for between 2 and 15 years
• Intakes of total dairy, low-fat dairy and milk were all
linearly associated with a lower risk of hypertension
• Consumption of high-fat dairy, total fermented dairy,
yoghurt and cheese not significantly associated with
hypertension incidence
Hypertension: Mechanisms
• Dairy products are low in sodium and
rich in protein, minerals (calcium,
magnesium, potassium and
phosphorus), vitamins (riboflavin,
folate, and vitamin D in fortified milk)
and trace elements (iodine, selenium
and zinc), which may contribute to a
reduction in blood pressure individually
or in combination
• Although sodium is the mineral with the
most significant effect on blood
pressure, calcium and potassium also
play a role
McGrane et al., 2011; Kris-Etherton et al., 2009; Dickinson et al., 2006; Ralston et al., 2012;
FitzGerald et al., 2004; Huth et al., 2006
Hypertension: Mechanisms
McGrane et al., 2011; Kris-Etherton et al., 2009; Dickinson et al., 2006; Ralston et al., 2012;
FitzGerald et al., 2004; Huth et al., 2006
Bioactive milk peptides such as lactotripeptides may also
contribute to the protective effect of dairy on blood pressure
These compounds inhibit the action of angiotensin 1-
converting enzyme (ACE), thereby preventing blood vessel
constriction
The prebiotics and probiotics in dairy products may have a
positive effect on body weight and thus potentially also on the
comorbidities associated with overweight and obesity, of which
hypertension is one
Dental Caries
Dietary sugars contribute to the development of dental caries
• However, this does not act in isolation:
3 factors are required for dental caries to develop:
• the presence of dietary carbohydrate (sugar)
• dental plaque bacteria and
• teeth that are susceptible to caries
Aimutis, 2012
Ferment the sugar Produce an acid Dissolves enamel
Dental Caries• Sweetening power of lactose is only
15% that of sucrose - unlikely
sweetener choice in processed foods
• Dairy products contain proteins,
fats, vitamins and minerals
(calcium and phosphorus), which
protect against dental caries
• When replacing other sugars, such as
sucrose and fructose, lactose has
been shown to be the least
cariogenic of all dietary sugars
• Milk further also does not increase
plaque acidity
Merritt, 2006; Shenkin et al., 2003; Molan, 2001
Dental Caries: Evidence
Dror and Allen, 2014:
11 observational studies
• Association between dairy intake
and health outcomes in children and
adolescents in developed countries
• All studies reported an inverse
association between dairy intake
and dental caries and some reported
that the association was even
stronger for yoghurt and cheese
consumption
Dental Caries: Evidence
Adegboye et al.
(2012):
• Intake of calcium from
dairy sources
associated with a
reduced risk of tooth
loss, but the same
association was not
seen when calcium
from non-dairy sources
was consumed
Dental Caries: Evidence
Levine (2001):
• Consumption of sweetened
dairy foods, such as
chocolate milk, does not
increase the risk of dental
caries and therefore dairy
beverages are considered a
healthier option than
sweetened soft drinks
Dental Caries: Mechanisms
• Eating cheese increases the concentration
of calcium in saliva and plaque, which
helps to protect tooth enamel
• Bioactive peptides in caseins protect
against caries by preventing
demineralization and inhibiting the
attachment of bacteria to the teeth
• Probiotics in milk also result in lower
bacterial counts, possibly because the
composition of the salivary film changes
and there is reduced adhesion of bacteria
Merritt et al., 2006; Kashket and DePaola, 2002; Aimutis, 2004; Stamatova and Meurman,
2009
Dental Caries: Infant feeding
• Most infants are exposed to lactose during breastfeeding or
formula feeding and in the presence of cariogenic bacteria,
milk could potentially be cariogenic
• The reportedly higher cariogenecity of human milk (and
some infant formulas) compared with cow’s milk may be
due to the comparatively higher lactose content and lower
protein, calcium and phosphorus content in these milks
Koletzko et al., 2005
Dental Caries: Infant feeding
• When babies go to sleep with a
bottle, milk may remain in the
mouth for several hours, resulting
in decreased salivary flow and
extended exposure of dental
plaque to fermentable
carbohydrates
• Formulas that contain other
sweeteners, such as high-
fructose corn syrup or sucrose,
are also more cariogenic than
those containing only lactose
Koletzko et al., 2005
Dental Caries: Prevention
• Importance of oral health in preventing development of
caries
• Different foods can affect oral pH, plaque formation and
salivary flow
• Healthy eating has a critical role in the growth,
development and maintenance of oral tissues throughout
life
• Intake of milk and dairy products is an essential component
of healthy eating, and the calcium and bioactive
components in dairy may have an important role in
preventing dental caries and periodontitis
Aimutis, 2012; Merritt, 2006; Aimutis, 2004
Conclusion
There is extensive evidence that moderate consumption of
dairy, as part of a balanced diet, is beneficial to health!
References• Abargouei AS, Janghorban M, Salehi-Marzijarani M and Esmaillzadeh A. 2012. Effect of dairy consumption on
weight and body composition in adults: a systematic review and meta-analysis of randomized controlled
clinical trials. International Journal of Obesity, 36:1485–1493.
• Abrams SA, Griffin IJ, Davila PM. 2002. Calcium and zinc absorption from lactose-containing and lactose-free
infant formulas. American Journal of Clinical Nutrition, 76:442–446.
• Adegboye AR, Twetman S, Christensen LB and Heitmann BL. 2012. Intake of dairy calcium and tooth loss
among adult Danish men and women. Nutrition, 28:779–784.
• Ahmadi-Abhari S, Luben RN, Powell N, Bhaniani A, Chowdhury R, Wareham NJ, Forouhi NG and Khaw KT. 2013.
Dietary intake of carbohydrates and risk of type 2 diabetes: the European Prospective Investigation into
Cancer–Norfolk Study. British Journal of Nutrition, 23:1–11.
• Aimutis WR. 2004. Bioactive properties of milk proteins with particular focus on anticariogenesis. Journal of
Nutrition, 134:989S–995S.
• Aimutis WR. 2012. Lactose cariogenicity with an emphasis on childhood dental caries. International Dairy
Journal, 22:152–158.
• Amiri M, Diekmann L, von Köckritz-Blickwede M and Naim HY. 2015. The diverse forms of lactose intolerance
and the putative linkage to several cancers. Nutrients, 7:7209–7230.
References• Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser
MM, Lin P and Karanja N. 1997. A clinical trial of the effects of dietary patterns on blood pressure. New
England Journal of Medicine, 336(16):1117–1124.
• Areco V, Rivoira MA, Rodriguez V, Marchionatti AM, Carpentieri A and Tolosa de Talamoni N. 2015. Dietary and
pharmacological compounds altering intestinal calcium absorption in humans and animals. Nutrition Research
Reviews, 28:83–99.
• Aune D, Lau R, Chan DS, Vieira R, Greenwood DC, Kampman E and Norat T. 2012. Dairy products and
colorectal cancer risk: a systematic review and meta-analysis of cohort studies. Annals of Oncology, 23:37–45.
• Aune D, Norat T, Romundstad P and Vatten LJ. 2013. Dairy products and the risk of type 2 diabetes: a
systematic review and dose-response meta-analysis of cohort studies. American Journal of Clinical Nutrition,
98:1066-1083.
• Bailey RK, Pozo Fileti C, Keith J, Tropez-Sims S, Price W and Allison-Ottey SD. 2013. Lactose intolerance and
health disparities among African Americans and Hispanic Americans: an updated consensus statement. Journal
of the National Medical Association, 105(2):112–127.
• Bonneux L. 2014. Unaccounted sex differences undermine association between milk intake and risk of
mortality and fractures. British Medical Journal, 349:g7012.
• Brown-Esters O, Mc Namara P and Savaiano D. 2012. Dietary and biological factors influencing lactose
intolerance. International Dairy Journal, 22:98–103.
References• Cederlund A, Kai-Larsen Y, Printz G, Yoshio H, Alvelius G, Lagercrantz H, Strömberg R, Jörnvall H,
Gudmundsson GH and Agerberth B. 2013. Lactose in human breast milk an inducer of innate immunity with
implications for a role in intestinal homeostasis. PLoS One, 8:e53876.
• Charlton KE, Steyn K, Levitt NS, Zulu JV, Jonathan D, Veldman FJ and Nel JH. 2005. Diet and blood pressure in
South Africa: intake of foods containing sodium, potassium, calcium, and magnesium in three ethnic groups.
Nutrition, 21:39–50.
• Chen M, Pan A, Malik VS and Hu FB. 2012. Effects of dairy intake on body weight and fat: a meta-analysis of
randomized controlled trials. American Journal of Clinical Nutrition, 96:735–747.
• Chichlowski M, German JB, Lebrilla CB and Mills DA. 2011. The influence of milk oligosaccharides on
microbiota of infants: opportunities for formulas. Annual Review of Food Science and Technology, 2:331–351.
• Christensen R, Lorenzen JK and Svith CR. 2009. Effect of calcium from dairy and dietary supplements on
faecal fat excretion: a meta-analysis of randomized controlled trials. Obesity Reviews, 10:475–486.
• Coelho AI, Berry GT and Rubio-Gozalbo ME. 2015. Galactose metabolism and health. Current Opinion in
Clinical Nutrition and Metabolic Care, 18:422–427.
• Cramer DW. 1989. Lactase persistence and milk consumption as determinants of ovarian cancer risk. American
Journal of Epidemiology, 130:904–910.
References• Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J, Packer L and Liu J. 2006. Chronic systemic D-galactose exposure
induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic
acid. Journal of Neuroscience Research, 83:1584–1590.
• Daubioul C, Rousseau N, Demeure R, Gallez B, Taper H, Declerck B and Delzenne N. 2002. Dietary fructans,
but not cellulose, decrease triglyceride accumulation in the liver of obese Zucker fa/fa rats. Journal of
Nutrition, 132:967–973.
• Dauchet L, Kesse-Guyot E, Czernichow S, Bertrais S, Estaquio C, Peneau S, Vergnaud A, Chat-Yung S, Castetbon
K, Deschamps V, Brindel P and Hercberg S. 2007. Dietary patterns and blood pressure change over 5-y follow-
up in the SU.VI.MAX cohort. American Journal of Clinical Nutrition, 85:1650–1656.
• Décombaz J, Jentjens R, Ith M, Scheurer E, Buehler T, Jeukendrup A and Boesch C. 2011. Fructose and
galactose enhance postexercise human liver glycogen synthesis. Medicine and Science in Sports and Exercise,
43:1964–1971.
• Deng Y, Misselwitz B, Ning D and Fox M. 2015. Lactose Intolerance in adults: biological mechanism and dietary
management. Nutrients, 7:8020–8035.
• Dickinson HO, Nicolson DJ, Cook JV, Campbell F, Beyer FR and Mason J. 2006. Calcium supplementation for the
management of primary hypertension in adults. Cochrane Database Systematic Review, 19(2):CD004639.
References• Dong JY, Zhang L, He K and Qin LQ. 2011. Dairy consumption and risk of breast cancer: a meta-analysis of
prospective cohort studies. Breast Cancer Research and Treatment, 127:23–31.
• Dror K. 2014. Dairy consumption and pre-school, school-age and adolescent obesity in developed countries: a
systematic review and meta-analysis. Obesity Reviews, 15:516–527.
• Dror DK and Allen LH. 2014. Dairy product intake in children and adolescents in developed countries: trends,
nutritional contribution, and a review of association with health outcomes. Nutrition Reviews, 72:68–81.
• Duthie SJ. 2011. Folate and cancer: how DNA damage, repair and methylation impact on colon carcinogenesis.
Journal of Inherited Metabolic Disorders, 34:101–109.
• Eiwegger T, Stahl B, Schmitt J, Boehm G, Gerstmayr M, Pichler J, Dehlink E, Loibichler C, Urbanek R and
Szepfalusi Z. 2004. Human milk-derived oligosaccharides and plant-derived oligosaccharides stimulate
cytokine production of cord blood T-cells in vitro. Pediatric Research, 56:536–540.
• Elwood PC, Givens DI, Beswick AD, Fehily AM, Pickering JE and Gallacher J. 2008. The survival advantage of
milk and dairy consumption: an overview of evidence from cohort studies of vascular diseases, diabetes and
cancer. Journal of the American College of Nutrition, 27:723S–7234S.
• Emms T. 2005. Galactose Content of Foods, BIOSCREEN Specialist Medical Testing Laboratory.
www.bioscreenmedical.com. Accessed on 3 May 2016.
• FitzGerald RJ, Murray BA and Walsh DJ. 2004. Hypotensive peptides from milk proteins. Journal of Nutrition,
134:980S–988S.
References• Flint HJ, Scott KP, Louis P and Duncan SH. 2012.The role of the gut microbiota in nutrition and health. Nature
Reviews Gastroenterology & Hepatology, 9(10):577–589.
• Gao D, Ning N, Wang C, Wang Y, Li Q, Meng Z, Liu Y and Li Q. 2013. Dairy products consumption and risk of
type 2 diabetes: systematic review and dose-response meta-analysis. PLoS ONE, 8(9):e73965.
• Genkinger JM, Hunter DJ, Spiegelman D, Anderson KE, Arslan A, Beeson WL, Buring JE, Fraser GE,
Freudenheim JL, Goldbohm RA, Hankinson SE, Jacobs Jr. DR, Koushik A, Lacey Jr. JV, Larsson SC, Leitzmann M,
McCullough ML, Miller AB, Rodriguez C, Rohan TE, Schouten LJ, Shore R, Smit E, Wolk A, Zhang SM and Smith-
Warner SA. 2006. Dairy products and ovarian cancer: a pooled analysis of 12 cohort studies. Cancer
Epidemiology, Biomarkers & Prevention, 15(2):364–372.
• Goldfein KR and Slavin JL. 2015. Why sugar is added to food: food science 101. Comprehensive Reviews in
Food Science and Food Safety, 14(5):644–656.
• Gopal PK and Gill HS. 2000. Oligosaccharides and glycoconjugates in bovine milk and colostrum. British
Journal of Nutrition, 84(1):S69–S74.
• Guggenblichler JP, De Bettignies-Dutz A, Meissner S and Jurenitsch J. 1997. Acid oligosaccharides from natural
sources block adherence of Escherichia coli on uropithelial cells. Pharmaceutical and Pharmacological Letters,
7:35–38.
• Gunnerud U, Holst JJ, Östman E and Björk I. 2012. The glycemic, insulinemic and plasma amino acid responses
to equi-carbohydrate milk meals, a pilot-study of bovine and human milk. Nutrition Journal, 11:83.
References• Hanover LM and White JS. 1993. Manufacturing, composition, and application of fructose. Journal of Clinical
Nutrition, 58:724s–732s.
• Heaney RP. 2013. Dairy intake, dietary adequacy, and lactose intolerance. Advances in Nutrition, 4:151–156.
• Heaney RP and Nordin BEC. 2002. Calcium effects on phosphorus absorption: implications for the prevention
and co-therapy of osteoporosis. Journal of the American College of Nutrition, 21:239–244.
• Hickey RM. 2012. The role of oligosaccharides from human milk and other sources in prevention of pathogen
adhesion. International Dairy Journal, 22:141–146.
• Hill TR. 2014. Vitamin D status, bone fracture, and mortality. British Medical Journal, 349:g6995.
• Hirahatake KM, Slavin JL, Makic KC and Adams SH. 2014. Associations between dairy foods, diabetes, and
metabolic health: potential mechanisms and future directions. Metabolism, 63:618–627.
• Huang LY, Wahlqvist ML, Huang YC and Lee MS. 2014. Optimal dairy intake is predicated on total,
cardiovascular, and stroke mortalities in a Taiwanese cohort. Journal of the American College of Nutrition,
33:426–436.
• Huth PJ, DiRienzo DB and Miller GD. 2006. Major scientific advances with dairy foods in nutrition and health.
Journal of Dairy Science, 89:1207–1221.
• Kalergis M, LeungYinko SSL and Nedelcu R. 2013. Dairy products and prevention of type 2 diabetes:
implications for research and practice. Frontiers in Endocrinology, 4(90):1–6.
References• Kashket S and DePaola DP. 2002. Cheese consumption and the development and progression of dental caries. Nutrition
Reviews, 60:97–103.
• Keast DR, Fulgoni VL, Nicklas TA and O'Neil CE. 2013. Food sources of energy and nutrients among children in the
United States: National Health and Nutrition Examination Survey 2003–2006. Nutrients, 5(1):283–301.
• Keith JN, Nicholls J, Reed A, Kafer K and Miller GD. 2011. The prevalence of self-reported lactose intolerance and the
consumption of dairy foods among African American adults are less than expected. Journal of the National Medical
Association, 103:36–45.
• Koletzko B, Baker S, Cleghorn G, Neto UF, Gopalan S, Hernell O, Hock QS, Jirapinyo P, Lonnerdal B, Pencharz P,
Pzyrembel H, Ramirez-Mayans J, Shamir R, Turck D, Yamashiro Y and Zong-Yi D. 2005. Global standards for the
composition of infant formula: recommendations of an ESPGHAN coordinated international expert group. Journal of
Pediatric Gastroenterology and Nutrition, 41:584e599.
• Koralek DO, Bertone-Johnson ER, Leitzmann MF, Sturgeon SR, Lacey JV, Schairer Cand Schatzkin A. 2006. Relationship
between calcium, lactose, vitamin D, and dairy products and ovarian cancer. Nutrition and Cancer, 56:22–30.
• Kratz M, Baars T and Guyenet S. 2013. The relationship between high-fat dairy consumption and obesity,
cardiovascular, and metabolic disease. European Journal of Nutrition, 52:1–24.
• Kris-Etherton PM, Grieger JA, Hilpert KF and West SG. 2009. Milk products, dietary patterns and blood pressure
management. Journal of the American College of Nutrition, 28(1):103S–119S.
References• Kuntz S, Kunz C and Rudloff S. 2009. Oligosaccharides from human milk induce growth arrest via G2/M by influencing
growth-related cell cycle genes in intestinal epithelial cells. British Journal of Nutrition, 101:1306–1315. Kwak H, Lee W
and Lee M. 2012. Revisiting lactose as an enhancer of calcium absorption. International Dairy Journal, 22:147e151.
• Labos C and Brophy J. 2014. Statistical problems with study on milk intake and mortality and fractures. British Medical
Journal, 349:g6991.
• Lamprecht SA and Lipkin M. 2001. Cellular mechanisms of calcium and vitamin D in the inhibition of colorectal
carcinogenesis. Annals of the New York Academy of Sciences, 952:73–87.
• Lee M, Wahlqvist ML and Peng C. 2015.Dairy foods and health in Asians: Taiwanese considerations. Asia Pacific Journal of
Clinical Nutrition, 24(1):S14–S20.
• Lempert SM, Christensen LB, Froberg K, Raymond K and Heitmann BL. 2015. Association between dairy intake and caries
among children and adolescents. Results from the Danish EYHS follow-up study. Caries Research, 49:251–258.
• Leonardi M, Gerbault P, Thomas M and Burger J. 2012. The evolution of lactase persistence in Europe. A synthesis of
archaeological and genetic evidence. International Dairy Journal, 22:88–97.
• Levine RS. 2001. Milk, flavoured milk products and caries. British Dental Journal, 191:20.
• Li F, An SL, Zhou Y, Liang ZK, Jiao ZJ, Jing YM, Wan P, Shi XJ and Tan WL. 2011. Milk and dairy consumption and risk of
bladder cancer: a meta-analysis. Urology, 78:1298–1305.
• Louie JC, Flood VM, Hector DJ, Rangan AM and Gill TP. 2011. Dairy consumption and overweight and obesity: a
systematic review of prospective cohort studies. Obesity Reviews, 12:e582–592.
References• Lu L, Xun P, Wan Y, He K and Cai W. 2016. Long-term association between dairy consumption and risk of
childhood obesity: a systematic review and meta-analysis of prospective cohort studies. European Journal of
Clinical Nutrition, 70(4):414–423.
• Lukito W, Malik SG, Surono IS and Wahlqvist ML. 2015. From ‘lactose intolerance’ to ‘lactose nutrition’. Asia
Pacific Journal of Clinical Nutrition, 24(1):S1–S8.
• Mao QQ, Dai Y, Lin YW, Qin J, Xie LP and Zheng XY. 2011. Milk consumption and bladder cancer risk: a meta-
analysis of published epidemiological studies. Nutrition and Cancer, 63:1263–1271.
• Mattar R, de Campos Mazo DF and Carrilho FJ. 2012. Lactose intolerance: diagnosis, genetic, and clinical
factors. Clinical and Experimental Gastroenterology, 5:113–121.
• McGrane MM, Essery E, Obbagy J, Lyon J, MacNeil P, Spahn J and Van Horn L. 2011. Dairy consumption, blood
pressure, and risk for hypertension: An evidence-based review of recent literature. Current Cardiovascular Risk
Reports, 5(4):287–298.
• McSweeney PLH and Fox PF (eds.) 2009. Advanced Dairy Chemistry, Vol. 3: Lactose, Water, Salts and Vitamins,
3rd edn. New York: Springer.
• Merritt J, Qi F and Shi W. 2006. Milk helps build strong teeth and promotes oral health. Journal of the
California Dental Association, 34:361–366.
• Michaëlsson K, Wolk A, Langenskiöld S, Basu S, Warensjö Lemming E, Melhus H and Byberg L. 2014. Milk intake
and risk of mortality and fractures in women and men: cohort studies. British Medical Journal, 349:g6015.
References• Missmer SA, Smith-Warner SA, Spiegelman D, Yaun SS, Adami HO, Beeson WL, van den Brandt PA, Fraser GE,
Freudenheim JL, Goldbohm RA, Graham S, Kushi LH, Miller AB, Potter JD, Rohan TE, Speizer FE, Toniolo P, Willett WC,
Wolk A, Zeleniuch-Jacquotte A and Hunter DJ. 2002. Meat and dairy food consumption and breast cancer: a pooled
analysis of cohort studies. International Journal of Epidemiology, 31:78–85.
• Molan PC. 2001. The potential of honey to promote oral wellness. General Dentistry, 49:584e589.
• Moorman PG and Terry PD. 2004. Consumption of dairy products and the risk of breast cancer: a review of the
literature. American Journal of Clinical Nutrition, 80:5–14.
• Moya M, Cortes E, Ballester MI, Vento M and Juste M. 1992. Short-term polycose substitution for lactose reduces calcium
absorption in healthy term babies. Journal of Pediatric Gastroenterology and Nutrition, 14:57–61.
• Mozaffarian D, de Oliveira Otto MC, Lemaitre RN, Fretts AM, Hotamisligil G, Tsai MY, Siscovick DS and Nettleton JA.
2013. trans-Palmitoleic acid, other dairy fat biomarkers, and incident diabetes: the Multi-Ethnic Study of Atherosclerosis
(MESA). American Journal of Clinical Nutrition, 97(4):854–861.
• Murphy N, Norat T, Ferrari P, Jenab M, Bueno-de-Mesquita B, Skeie G, Olsen A, Tjønneland A, Dahm CC, Overvad K,
Boutron-Ruault MC, Clavel-Chapelon F, Nailler L, Kaaks R, Teucher B, Boeing H, Bergmann MM, Trichopoulou A, Lagiou P,
Trichopoulos D, Palli D, Pala V, Tumino R, Vineis P, Panico S, Peeters PH, Dik VK, Weiderpass E, Lund E, Garcia JR,
Zamora-Ros R, Pérez MJ, Dorronsoro M, Navarro C, Ardanaz E, Manjer J, Almquist M, Johansson I, Palmqvist R, Khaw KT,
Wareham N, Key TJ, Crowe FL, Fedirko V, Gunter MJ and Riboli E. 2013. Consumption of dairy products and colorectal
cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).. PLoS ONE, 8:e72715.
References• Norat T and Riboli E. 2003. Dairy products and colorectal cancer: a review of possible mechanisms and
epidemiological evidence. European Journal of Clinical Nutrition, 57:1–17.
• Pal S, Ellis V and Dhaliwal S. 2010. Effects of whey protein isolate on body composition, lipids, insulin and
glucose in overweight and obese individuals. British Journal of Nutrition, 104:716–723.
• Panwar H, Rashmi HM, Batish VK and Grover S. 2013. Probiotics as potential biotherapeutics in the
management of type 2 diabetes — prospects and perspectives. Diabetes/Metabolism Research and Reviews,
29(2):103–112.
• Park Y, Leitzmann MF, Subar AF, Hollenbeck A and Schatzkin A. 2009. Dairy food, calcium, and risk of cancer in
the NIH-AARP Diet and Health Study. Archives of Internal Medicine, 169:391–401.
• Pereira PC. 2014. Milk nutritional composition and its role in human health. Nutrition, 30:619–627.
• Petschow B, Doré J, Hibberd P, Dinan T, Reid G, Blaser M, Cani PD, Degnan FH, Foster J, Gibson G, Hutton J,
Klaenhammer TR, Ley R, Nieuwdorp M, Pot B, Relman D, Serazin A and Sanders ME. 2013. Probiotics,
prebiotics, and the host microbiome: the science of translation. Annals of the New York Academy of Sciences,
1306:1–17.
• Pittas AG, Lau J, Hu FB and Dawson-Hughes B. 2007. The role of vitamin D and calcium in type 2 diabetes. A
systematic review and meta-analysis. Journal of Clinical Endocrinology and Metabolism, 92: 2017–2029.
References• Prado EL and Dewey KG. 2014. Nutrition and brain development in early life. Nutrition Reviews, 72:267–284.
• Ralston RA, Lee JH, Truby H, Palermo CE and Walker KZ. 2012. A systematic review and meta-analysis of
elevated blood pressure and consumption of dairy foods. Journal of Human Hypertension, 26:3–13.
• Rautiainen S, Wang L, Lee I, Manson JE, Buring JE and Sesso HD. 2016. Dairy consumption in association with
weight change and risk of becoming overweight or obese in middle-aged and older women: a prospective
cohort study. American Journal of Clinical Nutrition, 103:979-88.
• Rice BH, Quann EE and Miller GD. 2013. Meeting and exceeding dairy recommendations: effects of dairy
consumption on nutrient intakes and risk of chronic disease. Nutrition Reviews, 71:209–223.
• Rodriguez C, McCullough ML, Mondul AM, Jacobs EJ, Fakhrabadi-Shokoohi D, Giovannucci EL, Thun MJ and
Calle EE. 2003. Calcium, dairy products, and risk of prostate cancer in a prospective cohort of United States
men. Cancer Epidemiology, Biomarkers and Prevention, 12:597–603.
• Sanders TA. 2012. Role of dairy foods in weight management. American Journal of Clinical Nutrition, 96:687–
688.
• Schaafsma G. 2008. Lactose and lactose derivatives as bioactive ingredients in human nutrition. International
Dairy Journal, 18:458–465.
• Scrimshaw NS and Murray EB. 1988. The acceptability of milk and milk products in populations with a high
prevalence of lactose intolerance. American Journal of Clinical Nutrition, 48:1080–1159.
References• Shahar DR, Schwarzfuchs D, Fraser D, Vardi H, Thiery J, Fiedler GM, Bluher M, Stumvoll M, Stampfer MJ and Shai I. 2010.
Dairy calcium intake, serum vitamin D, and successful weight loss. American Journal of Clinical Nutrition, 92:1017–1022.
• Shaw JH, Schweigert BS, McIntire JM, Elvehjem CA and Phillips PH. 1944. Dental caries in the cotton rat. I. Methods of
study and preliminary nutritional experiments. Journal of Nutrition, 28:333–345.
• Shenkin JD, Heller KE, Warren JJ and Marshall TA. 2003. Soft drink consumption and caries risk in children and
adolescents. General Dentistry, 51:30–36.
• Sluijs I, Forouhi NG, Beulens JW, van der Schouw YT, Agnoli C, Arriola L, Balkau B, Barricarte A, Boeing H, Bueno-de-
Mesquita HB, Clavel-Chapelon F, Crowe FL, de Lauzon-Guillain B, Drogan D, Franks PW, Gavrila D, Gonzalez C, Halkjaer
J, Kaaks R, Moskal A, Nilsson P, Overvad K, Palli D, Panico S, Quirós JR, Ricceri F, Rinaldi S, Rolandsson O, Sacerdote C,
Sánchez MJ, Slimani N, Spijkerman AM, Teucher B, Tjønneland A, Tormo MJ, Tumino R, van der A DL, Sharp SJ,
Langenberg C, Feskens EJ, Riboli E, Wareham NJ; InterAct Consortium. 2012. The amount and type of dairy product
intake and incident type 2 diabetes: results from the EPIC-Interact study. American Journal of Clinical Nutrition, 96:382–
390.
• Soedamah-Muthu SS, Ding EL, Al-Delaimy WK, Hu FB, Engberink MF, Willett WC and Geleijnse JM. 2011. Milk and dairy
consumption and incidence of cardiovascular diseases and all-cause mortality: dose-response meta-analysis of
prospective cohort studies. American Journal of Clinical Nutrition, 93:158–171.
• Soedamah-Muthu SS, Verberne LDM, Ding EL, Engberink MF and Geleijnse JM. 2012. Dairy consumption and incidence of
hypertension: A dose-response meta-analysis of prospective cohort studies. Hypertension, 60:1131–1137.
References• Soedamah-Muthu SS, Verberne LDM, Ding EL, Engberink MF and Geleijnse JM. 2012. Dairy consumption and
incidence of hypertension: A dose-response meta-analysis of prospective cohort studies. Hypertension,
60:1131–1137.
• Sousa GT, Lira FS, Rosa JC, de Oliveira EP, Oyama LM, Santos RV and Pimentel GD. 2012. Dietary whey protein
lessens several risk factors for metabolic diseases: a review. Lipids in Health and Disease, 11:67.
• Stamatova I and Meurman JH. 2009. Probiotics and periodontal disease. Periodontology, 51(1):141–151.
• Suchy FJ, Brannon PM, Carpenter TO, Fernandez JR, Gilsanz V, Gould JB, Hall K, Hui SL, Lupton J, Mennella J,
Miller NJ, Osganian SK, Sellmeyer DE and Wolf MA. 2010. National Institutes of Health Consensus Conference:
lactose intolerance and health. Annals of Internal Medicine, 152:792–796.
• Sundar S. 2014. Milk and mortality: the potential effects of modern milk production. British Medical Journal,
349:g7006.
• Szilagyi A, Nathwani U, Vinokuroff C, Correa JAA and Shrier I. 2006. The effect of lactose maldigestion on the
relationship between dairy food intake and colorectal cancer: A systematic review. Nutrition and Cancer,
55:141–150.
• Tao N, DePeters EJ, German JB, Grimm R and Lebrilla CB. 2009. Variations in bovine milk oligosaccharides
during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass
spectrometry. Journal of Dairy Science, 92:2991–3001.
References• Tong X, Dong JY, Wu ZW, Li W and Qin LQ. 2011. Dairy consumption and risk of type 2 diabetes mellitus: a meta-analysis
of cohort studies. European Journal of Clinical Nutrition, 65:1027–1031.
• United States Department of Agriculture (USDA). 2010. Report of the dietary guidelines advisory committee on the
dietary guidelines for Americans 2010 to the Secretary of Health and Human Services and the Secretary of Agriculture.
Washington, DC: USDA.
• Vandenplas Y. 2015. Lactose intolerance. Asia Pacific Journal of Clinical Nutrition, 24(1):S9–S13.
• Velagapudi VR, Hezaveh R, Reigstad CS, Gopalacharyulu P, Yetukuri L, Islam S, Felin J, Perkins R, Borén J, Oresic M and
Bäckhed F. 2010. The gut microbiota modulates host energy and lipid metabolism in mice. Journal of Lipid Research,
51:1101–1112.
• Venema K. 2012. Intestinal fermentation of lactose and prebiotic lactose derivatives, including human milk
oligosaccharides. International Dairy Journal, 22:123–140.
• Visioli F and Strata A. 2014. Milk, dairy products, and their functional effects in humans: a narrative review of recent
evidence. Advances in Nutrition, 5:131–143.
• Vulevic J, Juric A, Walton GE, Claus SP, Tzortzis G, Toward RE and Gibson GR. 2015. Influence of galactooligosaccharide
mixture (B-GOS) on gut microbiota, immune parameters and metabonomics in elderly persons. British Journal of
Nutrition, 114:586–595.
• Wahlqvist ML. 2014. Ecosystem health disorders – changing perspectives in clinical medicine and nutrition. Asia Pacific
Journal of Clinical Nutrition, 23:1–15.
References• Waisbren SE, Potter NL, Gordon CM, Green RC, Greenstein P, Gubbels CS, Rubio-Gozalbo E, Schomer D, Welt C,
Anastasoaie V, D’Anna K, Gentile J, Guo CY, Hecht L, Jackson R, Jansma BM, Li Y, Lip V, Miller DT, Murray M, Power L,
Quin N, Rohr F, Shen Y, Skinder-Meredith A, Timmers I, Tunick R, Wessel A, Wu BL, Levy H, Elsas L and Berry GT. 2012.
The adult galactosemic phenotype. Journal of Inherited Metabolic Disease, 35:279–286.
• Weaver CM. 2014. How sound is the science behind the dietary recommendations for dairy? American Journal of Clinical
Nutrition, 99:1217S–1222S.
• Wilt TJ, Shaukat A, Shamliyan T, Taylor BC, MacDonald R, Tacklind J, Rutks I, Schwarzenberg SJ, Kane RL and Levitt M.
2010. Lactose intolerance and health. Evidence report/technology assessment (Full Report), 192:1–410.
• Wu Q, Cheung CKW and Shah NP. 2015. Towards galactose accumulation in dairy foods fermented by conventional starter
cultures: Challenges and strategies. Trends in Food Science & Technology, 41:24–36.
• Zemel MB. 2009. Proposed role of calcium and dairy food components in weight management and metabolic health. The
Physician & Sports Medicine, 2(37):1–12.
• Zivkovic AM and Barile D. 2011. Bovine milk as a source of functional oligosaccharides for improving human health.
Advances in Nutrition, 2:284–289.
• Zong G, Sun Q, Yu D, Zhu J, Sun L, Ye X, Li H, Jin Q, Zheng H, Hu FB and Lin X. 2014. Dairy consumption, type 2
diabetes, and changes in cardiometabolic traits: a prospective cohort study of middle-aged and older Chinese in Beijing
and Shanghai. Diabetes Care, 37:56–63.